Adhesive bandages and wound dressings for use by the consumer to treat/dress acute wounds or skin irritations are not new. A seen in FIG. 1, such adhesive bandages 10 are generally passive, in that they offer little or no chemical treatment for wound healing. Rather, they primarily serve to exert low levels of pressure on the wound, protect the wound from exposure to the environment, and absorb any exudates, which are produced from the wound site.
Typically, such bandages include a base layer 20, which is the layer seen by the consumer following application of the bandage to the wound. Such layer is typically formed from a polymeric material such as a film, nonwoven web, or combination thereof, and may be perforated in some fashion to allow for flexibility and/or further breathability. Such layer often includes a film component, having a top side surface 21, which is seen by the consumer after application of the bandage to the wound site, and a bottom side surface (skin contacting surface) 22. A skin-friendly adhesive 30 is usually placed over the base layer bottom side surface to provide a means for attaching the bandage to the consumer. Alternatively, a separate adhesive tape is used to attach the bandage/wound dressing to the wound site, if the bandage/wound dressing is of the nonadhesive type. In the center of the base layer 20 bottom side surface 22 is traditionally positioned an absorbent pad 40 for absorbing exudates from the wound. Such absorbent pad is typically comprised of a nonwoven material, or alternatively a cellulosic wadding. The nonwoven material may be treated to be hydrophilic or may include superabsorbent materials. Finally, a non-stick perforated film layer 50 (exemplified by Delnet material) is normally positioned over the absorbent pad layer 40, to provide a barrier between the absorbent pad and the wound itself. This allows the wound fluid to move through the perforated layer without sticking to the wound site.
Such absorbent pads have provided some level of absorbency, however, since they often only hold fluid in pores between fibers, their ability to pull fluids from the surface of the wound is often compromised by limited capacity and by their inability to hold fluid when compressed. There is therefore a need for a bandage with an absorbent pad which continues to draw fluid from a wound after the bandage has remained on the wound, and which is capable of retaining or locking up fluid, even under compression, and which provides a moist environment for wound healing. There is a further need for a bandage absorbent pad, which demonstrates the ability to both pull fluid from a wound, but also to release a beneficial treatment agent to a wound. For the purposes of this application, the term “beneficial treatment agent” shall refer to a chemical agent that can be added to a bandage which actively promotes wound healing, such as for example, by providing an antimicrobial effect, or by providing a hemostatic effect to the wound site, or both. There is also a need for a bandage, which provides a multifunctional wound healing system utilizing one or more compounds.
Typically the absorbent pad in such bandage does not include any medicinal components, although comparatively recently, bandage manufacturers have started including antibiotic agents on or within bandages to encourage wound healing. Such agents may be coated on, or impregnated within the bandage. For instance, several products are currently being marketed which contain an antiseptic benzalkonium chloride and an antibiotic mixture of polymixin B-sulfate and bacitracin-zinc. Further, patents in this area of technology have described the use of commonly known antiseptics and antibiotics, such as those described in U.S. Pat. Nos. 4,192,299, 4,147,775, 3,419,006, 3,328,259, and 2,510,993. Unfortunately, certain individuals have proven to be allergic to antibiotics, and as such, these bandages cannot be freely used by all consumers. Furthermore, there has recently been a push in the medical community to avoid excessive use of antibiotics so as to eliminate the risk that certain bacteria may become resistant to such medications. There is therefore a need in the bandage field for a bandage that offers healing agents to a wound, that are not associated with allergic responses. That is, there is a need in the bandage/wound dressing field for a wound dressing which encourages rapid healing as well as retards bleeding and/or infection.
It has not been new for bandages to accomplish hemostatic functions. For instance, W099/59647 describes a multilayered haemostatic bandage, which comprises preferably a thrombin layer between two fibrinogen layers. The dressing may contain other resorbable materials such as glycolic acid or lactic acid based polymers or copolymers. A hemostatic bandage is also disclosed in W0/97/28832. As in the previous reference, such bandage utilizes thrombin, in connection with fibrinogen, adhered to a fibrous matrix. While such bandages absorb fluid to a certain extent, they are directed to a hemostatic function.
U.S. Pat. No. 5,800,372 describes a field dressing for control of exsanguination. Such dressing describes the use of microfibrillar collagen and a superabsorbent polymer in a hemostatic bandage, which both absorbs blood and induces clotting. Such superabsorbent materials are fairly costly and significantly add to the cost of the wound dressing. Still further hemostatic bandages are disclosed in U.S. Pat. No. 4,616,644, and EP 0206697 A2, in which a thin coating of high molecular weight polyethyleneoxide is applied to the surface of a perforated plastic film wound release cover of an adhesive bandage. While such materials utilize polyethylene oxide in a bandage, such bandages do not appear to provide for the synergistic wound healing effect of such material with naturally occurring hemostatic and antimicrobial agents.
Poly(ethylene oxide) (“PEO”) is one of a very few polymers that is both water-soluble and thermally processable. PEO has also been shown to be biodegradable under a variety of conditions. Initial work has been done with PEO N-80 (molecular weight˜200,000) which is commercially available from Union Carbide. This grade of PEO is suitable for extrusion processing into film. However, the resultant films have relatively low tensile strength, low ductility, and brittleness. Typical values are 12 MPa break stress and elongation at break of 220%. In an unmodified form, high molecular weight PEO is not thermally processable. Melt fracture and excessive vaporization are observed as PEO is extruded. The resulting resins therefore cannot be cast into thin films, and do not have properties that are useful for bandage-type applications.
Additionally, recent development efforts have provided coating materials for a variety of uses. For example, U.S. Pat. No. 6,054,523, to Braun et al., describes materials that are formed from organopolysiloxanes containing groups that are capable of condensation, a condensation catalyst, an organopolysiloxane resin, a compound containing a basic nitrogen, and polyvinyl alcohol. The materials are reported to be suitable for use as hydrophobic coatings and for paints and sealing compositions.
Others have reported the production of graft copolymers having silane functional groups that permitted the initiation of cross-linking by exposure to moisture. Prejean (U.S. Pat. No. 5,389,728) describes a melt-processible, moisture-curable graft copolymer that was the reaction product of ethylene, a 1-8 carbon alkyl acrylate or methacrylate, a glycidyl containing monomer such as glycidyl acrylate or methacrylate, onto which has been grafted N-tert-butylaminopropyl trimethoxysilane. The resulting copolymers were reported to be useful as adhesives and for wire and cable coatings, however.
Furrer et al. in U.S. Pat. No. 5,112,919, reported a moisture-crosslinkable polymer that was produced by blending a thermoplastic base polymer, such as polyethylene, or a copolymer of ethylene, with 1-butene, 1-hexene, 1-octene, or the like; a solid carrier polymer, such as ethylene vinylacetate copolymer (EVA), containing a silane, such as vinyltrimethoxysilane; and a free-radical generator, such as an organic peroxide; and heating the mixture. The copolymers could then be cross-linked by reaction in the presence of water and a catalyst, such as dibutyltin dilaurate, or stannous octoate.
U.S. Pat. No. 4,593,071 to Keough reported moisture cross-linkable ethylene copolymers having pendant silane acryloxy groups. The resultant cross-linked polymers were reported to be especially resistant to moisture and to be useful for extruded coatings around wires and cables. The same group has reported similar moisture curable polymers involving silanes in U.S. Pat. Nos. 5,047,476, 4,767,820, 4,753,993, 4,579,913, 4,575,535, 4,551,504, 4,526,930, 4,493,924, 4,489,029, 4,446,279, 4,440,907, 4,434,272, 4,408,011, 4,369,289, 4,353,997, 4,343,917, 4,328,323, and 4,291,136. Since the cured products of these formulations are reported to be useful for coverings for wire and cable, and for non-conductive coatings for electrical conductors, it would be expected that they are durable coatings for which properties such as water absorbency and biodegradability would be a disadvantage.
Water-swellable polymers have reportedly been produced by cross-linking water soluble polymers, such as poly(ethylene oxide). It is known that poly(alkylene oxides), such as poly(ethylene oxide), can be cross-linked through gamma irradiation. Depending upon the degree of irradiation and the degree of cross-linking, the properties of the cross-linked polymer can range from a water soluble material to a hard solid with no appreciable water absorbency. Materials that are substantially non-water soluble, but still absorbent can be made. However, the use of gamma rays requires expensive equipment and time consuming procedures due to safety concerns, and the degree of cross-linking that is obtained is often difficult to control.
Several references have reported the use of chemical cross-linking groups as a method of avoiding the dangers and costs associated with the use of ionizing radiation. U.S. Pat. No.3,963,605 to Chu reported a water-swellable, cross-linked poly(alkylene oxide) that was produced by heating a mixture of poly(ethylene oxide) with acrylic acid and a free radical initiator such as acetyl peroxide in a hydrocarbon solvent such as hexane, heptane, or cyclohexane. Another alternative was reported in Canadian Pat. No. 756,190, and involved cross-linking through a di-vinyl monomer in the presence of a free radical catalyst. The use of other cross-linking agents, such as a diacrylate, or methyl-bis-acrylamide with a free radical inhibitor, have also been reported.
Lubricious coatings of cross-linked, hydrophilic polyurethane have been reported by Watson in U.S. Pat. No. 6,020,071. Another polyurethane coating is described by Tedeshchl et al., in EP 0992 252 A2, where a lubricious, drug-accommodating coating is described that is the product of a polyisocyanate; an amine donor, and/or a hydroxyl donor; and an isocyanatosilane adduct having terminal isocyanate groups and an alkoxy silane. A water soluble polymer, such as poly(ethylene oxide), can optionally be present. Cross-linking causes a polyurethane or a polyurea network to form, depending upon whether the isocyanate reacts with the hydroxyl donors or the amine donors. This composition provides lubricious benefits from a particular chemistry, which does not appear to provide high absorbency.
Chitosan is a deacetylated product of chitin (C8H13NO5)n, an abundant natural glucosamine polysaccharide found in the ecosystem. In particular, chitin is found in the shells of crustaceans, such as crabs, lobsters and shrimp. The compound is also found in the exoskeletons of marine zooplankton, in the wings of certain insects, such as butterflies and ladybugs, and in the cell wall of yeasts, mushrooms and other fungi.
In addition to being non-toxic, biocompatible and biodegradable, chitosan is also reported in the scientific literature to possess hemostatic, antimicrobial properties and other biomedical attributes. See for instance, Rev Macromol. Chem Phys., C40, 69-83 (2000), Chitin and Chitosan, Editors, G. Skjak-Braek, T. Anthonsen and P. Sanford, Elsevier, (1988); Chitin in Nature and Technology, Editors, R. Muzzarelli, C. Jeuniaux and G. W. Gooday, Plenum Press, (1986).
The biocompatibility of chitosan administered orally and intravenously has been assessed in animals. Its LD50 is over 16 g/Kg in mice, which is higher than for sucrose. LD50 is traditionally defined as the median lethal dose of a substance, which will kill 50% of the animals receiving that dose, with the dose being calculated on amount of material given per gram or kilogram of body weight, or amount per unit of body surface area. See for instance, the 18th Edition of Taber's Cyclopedic Medical Dictionary, p. 1085. The hemostatic properties of Chitosan have also been evaluated in the scientific literature in publications such as Ann. Thor. Surg., 35, 55-60, (1983); J Oral Maxillof Surg, 49, 858-63, (1991).
In recent years, however, attention has been directed in the research community towards biomedical applications of the chitosan compound. In this regard, the use of chitosan in the pharmaceutical and healthcare industry is currently being evaluated. For instance, use of chitosan has been reported in a pharmaceutical product in Pharm Res, 15, 1326-31, (1998). The use of chitosan in the pharmaceutical industry as an excipient has also been explored in Pharm Res, 15, 1326-31, (1998) and Drug Dev. Ind Pharm, 24, 979-93, (1998).
Antimicrobial properties of chitosan have been reported against Gram positive and Gram negative bacteria, including Streptococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Pseudomonas, Escherichia, Proteus, Klebsiella, Serratia, Acinobacter, Enterobacter and Citrobacter spp. See for instance, Muzzarelli et al., in Industrial Polysaccharides: Biomedical and Biotechnological Advances, Eds., V. Crescenzi and S. S. Stivala, Gordon and Breach, pp. 77-88, (1990) and Antimicr. Agents Chemoth., 34, 2019-24, (1990). See also, U.S. Pat. No. 4,659,700, which describes the use of Chitosan in a gel to be applied to wounds.
Chitosan has also been described in the literature to induce repair of tissue containing regularly arranged collagen bundles. See for instance Biomaterials, 9, 247-52, (1988). Additionally, non-woven fabrics made of chitosan fibers have been developed. See for instance, Eur. J. Plastic Surg., 10, 66-76, (1987). Further, chitin and chitosan derivatives have been studied for their antitumor effects. See for instance, Carbohydr. Res, 151, 403-8, (1986); and Chem. Pharm, 36, 784-90, (1988). Chitosan has additionally been reported as an effective immunomodulator in Vaccine, 4, 151-6, (1986); and K. Nishimura in Chitin Derivatives in Life Sciences, Ed., S. Tokura, Japan Chitin Soc., (1992).
Despite all of the research in the chitosan area, there is still a need for a practical application of chitosan that can benefit individuals on a daily basis, such as in the application to acute wounds obtained during a person's daily routine. Further, there is also a need for a wound healing system that takes advantage of the multiple medical benefits of chitosan in conjunction with other non-traditional wound healing chemistries.
While nicotinic acid (niacin), niacinamide (vitamin B3), ascorbic acid and niacinamide ascorbate are known as dietary supplements, for a variety of functions, it is not believed that such uses have been in conjunction with epidermal wound healing functions.
There is therefore a need for an improved bandage, which continues to provide absorbent capacity while compressed over a wound site. There is a further need for such an absorbent bandage/wound dressing, which allows for the release of wound healing agents while continuing to absorb exudates from the wound site. Further, there is a need of a bandage with an absorbent pad which is capable of retaining or locking up the fluid and which provides a moist environment for wound healing. Still further, there is a need for an adhesive bandage, which does not utilize traditional antibiotic treatment, but which does promote wound healing. Finally, there is a need for an adhesive bandage which promotes wound healing in multiple ways, but which does not utilize agents which may cause an allergic response in certain individuals, and does so at an affordable price point.